title: In vivo imaging of bone using a deep-red fluorescent molecular probe bearing multiple iminodiacetate groups.
abstract: Deep-red fluorescent molecular probes are described that have a dendritic molecular architecture with a squaraine rotaxane core scaffold and multiple peripheral iminodiacetate groups as the bone targeting units. Iminodiacetates have an inherently lower bone affinity than bisphosphonates, and a major goal of the study was to determine how many appended iminodiacetate groups are required for effective deep-red fluorescence imaging of bone in living rodents. A series of in vitro and in vivo imaging studies showed that a tetra(iminodiacetate) probe stains bones much more strongly than an analogous bis(iminodiacetate) probe. In addition, a control tetra(iminodipropionate) probe exhibited no bone targeting ability. The tetra(iminodiacetate) probe targeted the same regions of high bone turnover as the near-infrared bisphosphonate probe OsteoSense750. Longitudinal studies showed that the fluorescence image signal from living mice treated with the tetra(iminodiacetate) probe was much more stable over 19 days than the signal from OsteoSense750. The narrow emission band of the tetra(iminodiacetate) probe makes it very attractive for inclusion in multiplex imaging protocols that employ a mixture of multiple fluorescent probes in preclinical studies of bone growth or in fluorescence guided surgery. The results also suggest that molecules or nanoparticles bearing multivalent iminodiacetate groups have promise as bone targeting agents with tunable properties for various pharmaceutical applications.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , 236 Nieuwland Science Hall, Notre Dame, 46556 Indiana, United States.
authors.forename: Kara M
authors.initials: KM
authors.lastname: Harmatys
authors.forename: Erin L
authors.initials: EL
authors.lastname: Cole
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Smith
mesh_terms: D000818:Animals; D003503:Cyclobutanes / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry*; D007098:Imino Acids / Q000737:chemistry; D008297:Male; D051379:Mice; D010636:Phenols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D043862:Rotaxanes / Q000737:chemistry
chemical_list: D003503:Cyclobutanes; D005456:Fluorescent Dyes; D007098:Imino Acids; D010636:Phenols; D043862:Rotaxanes; C480596:squaraine; C008109:iminodiacetic acid